| Structural highlights
5v1a is a 2 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | ULP2, SMT4, YIL031W (Baker's yeast), CSM1, SPO86, YCR086W, YCR86W (Baker's yeast) |
| Activity: | Ulp1 peptidase, with EC number 3.4.22.68 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ULP2_YEAST] Insertion mutation in SMT4 confers temperature and benomyl sensitivity; high copy suppressor of a temperature sensitive mutation in MIF2. [CSM1_YEAST] Component of the monopolin complex which promotes monoorientation during meiosis I, required for chromosome segregation during meiosis. Plays also a mitotic role in DNA replication.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Post-translational modification by SUMO (small ubiquitin-like modifier) plays important but still poorly understood regulatory roles in eukaryotic cells, including as a signal for ubiquitination by SUMO targeted ubiquitin ligases (STUbLs). Here, we delineate the molecular mechanisms for SUMO-dependent control of ribosomal DNA (rDNA) silencing through the opposing actions of a STUbL (Slx5:Slx8) and a SUMO isopeptidase (Ulp2). We identify a conserved region in the Ulp2 C terminus that mediates its specificity for rDNA-associated proteins and show that this region binds directly to the rDNA-associated protein Csm1. Two crystal structures show that Csm1 interacts with Ulp2 and one of its substrates, the rDNA silencing protein Tof2, through adjacent conserved interfaces in its C-terminal domain. Disrupting Csm1's interaction with either Ulp2 or Tof2 dramatically reduces rDNA silencing and causes a marked drop in Tof2 abundance, suggesting that Ulp2 promotes rDNA silencing by opposing STUbL-mediated degradation of silencing proteins. Tof2 abundance is rescued by deletion of the STUbL SLX5 or disruption of its SUMO-interacting motifs, confirming that Tof2 is targeted for degradation in a SUMO- and STUbL-dependent manner. Overall, our results demonstrate how the opposing actions of a localized SUMO isopeptidase and a STUbL regulate rDNA silencing by controlling the abundance of a key rDNA silencing protein, Tof2.
Recruitment of a SUMO isopeptidase to rDNA stabilizes silencing complexes by opposing SUMO targeted ubiquitin ligase activity.,Liang J, Singh N, Carlson CR, Albuquerque CP, Corbett KD, Zhou H Genes Dev. 2017 Apr 15;31(8):802-815. doi: 10.1101/gad.296145.117. Epub 2017 May , 9. PMID:28487408[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rabitsch KP, Toth A, Galova M, Schleiffer A, Schaffner G, Aigner E, Rupp C, Penkner AM, Moreno-Borchart AC, Primig M, Esposito RE, Klein F, Knop M, Nasmyth K. A screen for genes required for meiosis and spore formation based on whole-genome expression. Curr Biol. 2001 Jul 10;11(13):1001-9. PMID:11470404
- ↑ Rabitsch KP, Petronczki M, Javerzat JP, Genier S, Chwalla B, Schleiffer A, Tanaka TU, Nasmyth K. Kinetochore recruitment of two nucleolar proteins is required for homolog segregation in meiosis I. Dev Cell. 2003 Apr;4(4):535-48. PMID:12689592
- ↑ Wysocka M, Rytka J, Kurlandzka A. Saccharomyces cerevisiae CSM1 gene encoding a protein influencing chromosome segregation in meiosis I interacts with elements of the DNA replication complex. Exp Cell Res. 2004 Apr 1;294(2):592-602. PMID:15023545 doi:10.1016/j.yexcr.2003.12.008
- ↑ Pan X, Ye P, Yuan DS, Wang X, Bader JS, Boeke JD. A DNA integrity network in the yeast Saccharomyces cerevisiae. Cell. 2006 Mar 10;124(5):1069-81. Epub 2006 Feb 16. PMID:16487579 doi:S0092-8674(06)00118-8
- ↑ Mekhail K, Seebacher J, Gygi SP, Moazed D. Role for perinuclear chromosome tethering in maintenance of genome stability. Nature. 2008 Dec 4;456(7222):667-70. doi: 10.1038/nature07460. Epub 2008 Nov 9. PMID:18997772 doi:10.1038/nature07460
- ↑ Liang J, Singh N, Carlson CR, Albuquerque CP, Corbett KD, Zhou H. Recruitment of a SUMO isopeptidase to rDNA stabilizes silencing complexes by opposing SUMO targeted ubiquitin ligase activity. Genes Dev. 2017 Apr 15;31(8):802-815. doi: 10.1101/gad.296145.117. Epub 2017 May , 9. PMID:28487408 doi:http://dx.doi.org/10.1101/gad.296145.117
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